title: Neonatal follicular Th cell responses are impaired and modulated by IL-4.
abstract: Newborns are characterized by poor responses to vaccines. Defective B cell responses and a Th2-type polarization can account for this impaired protection in early life. We in this study investigated the generation of follicular Th (TFH) cells, involved in the development of Ab response and germinal center reaction, upon vaccination in neonates. We showed that, compared with adults, Ab production, affinity maturation, and germinal center formation were reduced in neonates immunized with OVA-aluminum hydroxide. Although this vaccination induced CD4(+) CXCR5(+) PD-1(+) TFH cells in newborns, their frequency, as well as their Bcl6 expression and IL-21 and IL-4 mRNA induction, was decreased in early life. Moreover, neonatal TFH cells were mainly localized in interfollicular regions of lymphoid tissues. The prototypic Th2 cytokine IL-4 was found to promote the emergence and the localization in germinal centers of neonatal TFH cells, as well as the neonatal germinal center reaction itself. In addition, IL-4 dampened expression of Th17-related molecules in neonatal TFH cells, as TFH cells from immunized IL-4-deficient neonates displayed enhanced expression of RORγt and IL-17. This Th17-like profile correlated with an increased secretion of OVA-specific IgG2a. Our study thus suggests that defective humoral immunity in early life is associated with limited and IL-4-modulated TFH cell responses.
authors.affiliation: Institut d'Immunologie Médicale, Université Libre de Bruxelles, 6041 Gosselies, Belgium.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Debock
authors.forename: Kathy
authors.initials: K
authors.lastname: Jaworski
authors.forename: Hanan
authors.initials: H
authors.lastname: Chadlaoui
authors.forename: Sandrine
authors.initials: S
authors.lastname: Delbauve
authors.forename: Nicolas
authors.initials: N
authors.lastname: Passon
authors.forename: Laure
authors.initials: L
authors.lastname: Twyffels
authors.forename: Oberdan
authors.initials: O
authors.lastname: Leo
authors.forename: Véronique
authors.initials: V
authors.lastname: Flamand
mesh_terms: D000536:Aluminum Hydroxide / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D000915:Antibody Affinity / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology*; D000943:Antigens, Differentiation / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D018858:Germinal Center / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000096:biosynthesis; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor; D051560:Proto-Oncogene Proteins c-bcl-6; D054380:Receptors, CXCR5 / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D014611:Vaccination; D000098546:Interleukin-21
chemical_list: D000943:Antigens, Differentiation; C490010:Bcl6 protein, mouse; C513179:CXCR5 protein, mouse; D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; D020381:Interleukin-17; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D051560:Proto-Oncogene Proteins c-bcl-6; D054380:Receptors, CXCR5; D015847:Interleukin-4; D000536:Aluminum Hydroxide; D010047:Ovalbumin; D000098546:Interleukin-21